Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort

Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort Se Eun Park, Soseul Sung, Sangjun Lee, Youjin Hong, Woojin Lim, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7788690/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Colorectal cancer (CRC) is a significant and rising health burden globally and in Korea. While physical activity (PA) reduces CRC risk, evidence remains limited, especially in the Korean population. Additionally, the protective effect of PA may be modified by individual characteristics and is unclear in combination with sedentary behavior (SB). This study aimed to evaluate the association between PA and CRC risk in Korean populations, exploring subgroup-specific effects and the combined effect of PA and SB. Methods: Korean Multi-Center Cancer Cohort included 20,631 participants from various regions. Of these subjects, 4,675 men completed a PA-related questionnaire at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence risk were estimated using multivariable Cox proportional hazards models. Models were adjusted for age, cigarette smoking, educational level, alcohol drinking, and body mass index (BMI). Stratified analyses were performed by individual characteristics (e.g., age, BMI, and smoking status) to assess effect modification. The relationship was further assessed considering the joint effect of PA and SB. Results: Non-occupational PA (NOPA) level of 300-599 MET min/week was associated with a decreased risk of CRC (HR=0.14, 95% CI=0.04–0.61) compared to the inactive NOPA group. Stratified analyses revealed that NOPA level of 300-599 MET was linked to lowered CRC risk in age < 65 group, smokers and BMI < 25 group (HR=0.12, 95% CI=0.02–0.86; HR=0.08, 95% CI=0.01–0.60; HR=0.12, 95% CI=0.02–0.89, respectively). Additionally, combined analysis indicated that individuals with active NOPA and short SB had a significantly lower risk of CRC compared to those with inactive NOPA and prolonged SB (HR=0.25, 95% CI=0.08–0.83). Conclusions: This study indicates that NOPA of 300–599 MET min/week was associated with a reduced risk of CRC, particularly in younger individuals, smokers, and those with lower BMI. The protective effect was more evident when active NOPA was combined with short SB. These findings highlight PA as a modifiable factor in CRC prevention and the importance of incorporating individual characteristics into public health strategies. epidemiology colorectal neoplasms cohort studies physical activity subgroup analysis sedentary behavior Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Globally, colorectal cancer (CRC) ranks third in cancer incidence with more than 1.9 million new cases, and it is the second leading cause of cancer-related deaths [ 1 ]. By 2035, the number of CRC incidence is expected to increase by 80% [ 2 ]. In South Korea, CRC was the second most diagnosed cancer in 2021, showing an annual increase of 2.6% from 2019 to 2021 [ 3 ]. Numerous recent studies report a rising incidence of CRC among younger adults (under 50 years at diagnosis) in developed countries, highlighting the urgent need for further studies on the risk factors associated with CRC [ 4 ]. Physical activity (PA) has consistently been suggested as a risk reduction factor for CRC in previous studies [ 5 – 6 ]. PA is defined as any bodily movement that requires energy expenditure through the use of skeletal muscles and can be classified into four domains: leisure-time PA (LPA), occupational PA (OPA), domestic PA, and transportation PA [ 7 ]. Guidelines for PA emphasize LPA since it is known to be the most influential factor related to cancer incidence [ 8 ]. Several studies have demonstrated that an increase in moderate-to-vigorous LPA is associated with a reduced CRC risk [ 9 – 10 ]. However, evidence regarding how subgroup characteristics influence the association between PA and CRC, and how PA interacts with sedentary behavior (SB) in relation to CRC risk, remains limited. Demographic factors of study subjects, such as age, occupation and body mass index (BMI), should be considered as potential effect modifiers due to differences in PA distribution [ 11 ]. Most studies addressing PA as a protective factor against CRC have been conducted primarily in Western populations [ 12 – 13 ]. However, the association between PA and CRC may vary depending on individual characteristics, which differ between Western and Eastern populations [ 14 ]. Previous studies have identified racial disparities in CRC incidence linked to variations in risk factor prevalence and socioeconomic status [ 15 – 16 ]. These findings highlight the need for research specifically targeting Korean populations, where such risk factors may interact differently with PA. Stratification by lifestyle factors such as smoking, excess body weight and SB—major contributors to cancer burden in Korea—may clarify how these variables interact with PA in influencing CRC risk [ 17 – 19 ]. Overall, it is important to evaluate the association between PA and CRC in Korean populations, explore subgroup-specific associations through stratified analyses, and assess the combined effect of PA and SB on CRC risk. Given that PA is a modifiable lifestyle factor, identifying its protective effects across different risk profiles could contribute to reducing the burden of CRC in Korea [ 20 ]. Materials and Methods Study population and data collection This study was conducted within the Korean Multi-Center Cancer Cohort (KMCC) as a prospective cohort study. A total of 20,631 participants were enrolled from 1993 to 2005 across seven rural and urban areas in Korea: Haman, Uiryeong, Chuncheon, Chungju, Pohang, Uljin, and Changwon [21]. The subject selection flowchart for the total cohort is shown in Figure 1. We excluded participants with a history of cancer (n=623), insufficient information on BMI and PA (n=8,646) and women (n=6,687) because the number of CRC cases was insufficient for reliable statistical analyses. Consequently, the final cohort for analysis comprised 4,675 male subjects. Data on general lifestyle, PA, SB and agricultural exposure were collected through interviews conducted by trained interviewers using a structured questionnaire and anthropometric measurements were also gathered [22]. Incident cancer cases at KMCC were identified through record linkage with data from the National Cancer Registry. Exposure assessment: Physical activity and sedentary behavior Information on the level of PA was collected using an interview-based questionnaire. The questionnaire classified PA into three categories: vigorous non-occupational PA (NOPA), moderate NOPA and OPA. Vigorous NOPA included jogging, cycling uphill, playing tennis, participating in swimming competitions, and engaging in aerobic activities. Moderate NOPA included activities such as walking briskly, playing golf or bowling, riding a bicycle on level roads, gardening, cleaning, and doing laundry. OPA was defined as activities such as moving heavy furniture, loading and unloading trucks, shoveling, planting rice, and weeding. The questionnaire was designed to assess the level of PA based on activity time ranging from less than 0.5 hours per week to 31 hours or more per week. Metabolic equivalents of tasks (METs) were used to evaluate overall PA level. 1 MET is defined as 3.5 mL of oxygen uptake per kilogram per minute when a person is sitting quietly [23]. METs were calculated by multiplying the average number of minutes per week of each PA by the specific MET score according to the IPAQ standard [24]. Vigorous NOPA and OPA were assigned a value of 8 METs, while moderate NOPA was assigned a value of 4 METs. After estimating METs, respondents were categorized into quartiles based on the interquartile range of the distribution for NOPA: < 300 (reference), 300–599, 600–2,999, and ≥ 3,000. This approach allowed us to examine relationships across the full spectrum of activity levels observed in our cohort. For OPA, the highest category (≥ 3,000 MET minutes/week) was further divided at 9,000 MET minutes/week, resulting in the following categories: < 300 (reference), 300–599, 600–2,999, 3,000–8,999, and ≥ 9,000. For the analysis of the combined effects of PA and SB, PA was classified into two groups: inactive (< 300 MET min/week) and active (≥ 300 MET min/week). SB was defined based on self-reported television viewing time, with ≥ 6 hours/day categorized as prolonged and < 6 hours/day as short, according to previous studies [25,26]. Statistical analysis The baseline differences among four MET min/week groups were compared using linear regression for continuous variables and Cochran-Armitage test for categorical variables. Differences in mean age and BMI, along with occupation (farmer/non-farmer), cigarette smoking (never/ever), alcohol consumption (never/ever), educational level (≥ 9 years), family history of CRC, colon polyps or irritable bowel syndrome, diabetes, meat preference and dietary intake were evaluated. The Cox proportional hazards model was used to evaluate hazard ratios (HRs) and their 95% confidence intervals (95% CIs) for CRC incidence based on the level of PA. The following factors were selected as potential confounders in the model: (a) age, educational level, and BMI, which may affect lifestyle factors including PA; (b) cigarette smoking as a Group 1A carcinogenic agent according to the International Agency for Research on Cancer [27]; and (c) alcohol drinking as a risk factor for CRC with convincing evidence [28]. All statistical analyses were performed using R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria). Results Characteristics of study subjects and distribution of PA Selected characteristics are presented in Table 1. A significant trend was observed across NOPA levels (MET min/week) for occupation, smoking status, alcohol consumption and vegetable intake. Selected characteristics of the cohort population and CRC cases revealed differences in age, education level, diabetes diagnosis and meat preference (S1 Table). Low and high groups of NOPA and OPA categories also showed significant differences for several characteristics (S2 Table). There was a marked trend (p < 0.05) among different characteristics including age, BMI, occupation, smoking status, education level, diabetes diagnosis and vegetable intake across OPA levels (S3 Table). Farmers were more common in the NOPA > 90th percentile group compared with the lower percentile groups (S4 Table). The distribution of NOPA and OPA differed with the trend of NOPA showing a downward-sloping curve, whereas OPA exhibited an inverse J-shaped curve (S1 Figure). Association between PA and incidence of CRC Association between the PA level and incidence of CRC is presented in Table 2. In NOPA, the 300–599 MET min/week group was significantly associated with a reduced risk of CRC incidence (HR=0.14, 95% CI=0.04–0.61). OPA did not show any statistically significant relationships on CRC incidence. Figure 2 demonstrates that individuals in the 300–599 MET min/week of NOPA group had the lowest cumulative incidence of CRC relative to the other groups (p < 0.05). Further analyses are presented in Figures 3 to 5. As shown in Figure 3, restricted cubic spline analysis presented that the relationship between CRC incidence and NOPA differed from that with OPA. Figure 4 illustrates the stratified analysis of the association between PA and CRC incidence with HRs and 95% CIs in a forest plot. When NOPA was categorized into four groups (inactive as < 300, low as 300-599, moderate as 600-2,999 and high as ≥ 3,000 MET min/week), analyses by age, occupation, smoking status, and BMI revealed that the low Table 1. Selected characteristics of total participants in KMCC according to METs of NOPA Characteristics MET (min/week) < 300 300 – 599 600 – 2999 ≥ 3000 p for trend 1 Mean (SD) Mean (SD) Mean (SD) Mean (SD) Age 51.38 (15.16) 51.66 (15.93) 51.79 (15.89) 53.22 (13.01) 0.12 BMI 23.06 (3.14) 23.35 (3.14) 23.37 (3.00) 23.51 (2.93) 0.09 N (%) N (%) N (%) N (%) Farmer 606 (49.35) 241 (44.63) 757 (44.93) 691 (56.55) < 0.01 Ever-smoking 2 986 (80.29) 448 (82.96) 1,333 (79.11) 982 (80.36) < 0.01 Ever-alcohol drinking 953 (78.05) 398 (73.84) 1,259 (75.03) 927 (76.05) < 0.01 Education ≥ 9 years 497 (40.80) 211 (39.37) 817 (48.83) 639 (52.64) 0.06 Family history of CRC 10 (0.81) 6 (1.11) 15 (0.89) 12 (0.98) 0.54 Colon polyps or IBD 8 (0.65) 2 (0.37) 9 (0.53) 5 (0.41) 0.69 Diabetes 3 123 (10.02) 61 (11.30) 186 (11.04) 148 (12.11) 0.11 Meat preference 228 (55.61) 104 (56.52) 443 (59.70) 280 (60.22) 0.14 Dietary intake (time/week) Red meats ≥ 1 227 (57.32) 103 (59.54) 461 (65.39) 291 (69.62) 0.61 Vegetables ≥ 2.5 341 (69.31) 163 (73.09) 613 (72.80) 407 (76.94) < 0.01 Fruits ≥ 2.5 272 (52.71) 156 (59.54) 635 (67.55) 410 (69.02) 0.10 Abbreviations; KMCC, Korean Multi-center Cancer Cohort study; MET, Metabolic Equivalent of Task; NOPA, non-occupational physical activity; BMI, Body mass index; CRC, colorectal cancer; IBD, irritable bowel syndrome 1. Liner regression for continuous variables (age, BMI) and Cochran–Armitage trend test for categorical variables (farmer, cigarettes smoking, alcohol drinking, education ≥ 9 years, family history of CRC, colon polyps or IBD, diabetes, meat preference and dietary intake). 2. Ever-smoking is defined as past and current smoking more or equal to 400 cigarettes. 3. Diabetes was defined as ‘past diagnosis of diabetes mellitus’ or ‘fasting blood sugar > 125 mg/mL’. Table 2. Association between MET min/week of PA and CRC risk MET min/week Cohort Person-years Cancers N HR (95% CI) 1 NOPA < 300 15089 31 1.00 (reference) 300-599 6432 3 0.14 (0.04-0.61) 600-2999 20320 24 0.57 (0.03-2.43) ≥ 3000 15371 25 0.77 (0.04-3.25) OPA < 300 19484 28 1.00 (reference) 300-599 4903 5 1.06 (0.41-2.78) 600-2999 6145 9 1.06 (0.35-3.19) 3000-8999 7487 12 0.94 (0.33-2.66) ≥ 9000 19194 28 0.95 (0.36-2.46) Abbreviation: MET, Metabolic Equivalent of Task; PA, physical activity; CRC, colorectal cancer; NOPA, non-occupational physical activity; OPA, occupational physical activity 1. Adjusted for age, cigarette smoking, education, alcohol drinking and BMI. NOPA group was associated with a lower incidence of CRC among individuals aged < 65 years (HR=0.12, 95% CI=0.02–0.86), smokers (HR=0.08, 95% CI=0.01–0.60), and those with BMI < 25 (HR=0.12, 95% CI=0.02–0.89). Figure 5 illustrates the combined effect of PA and SB on CRC incidence; compared with participants who had inactive PA and prolonged SB, those with active PA and short SB showed a reduced risk of CRC (HR=0.25, 95% CI= 0.08–0.83). Discussion In this study of 4,675 male participants, we observed engaging in NOPA of 300–599 MET min/week was associated with a lower risk of CRC, while OPA showed no significant association. Stratified analyses further indicated that the protective effect of low NOPA in 300–599 MET min/week group was evident among individuals aged < 6 years, smokers, and those with BMI < 25. In addition, combined analysis revealed that participants with active PA and shorter SB had a reduced risk of CRC compared with those with inactive PA and prolonged sedentary time. The biological mechanisms underlying the association between PA and CRC involve obesity, IGF-1 signaling, chronic inflammation, and epigenetic regulation [29]. Physical inactivity contributes to abdominal obesity, reduced insulin sensitivity, and systemic inflammation, thereby increasing CRC risk [30]. Insufficient PA may also elevate circulating IGF-1, promoting abnormal cell proliferation and tumor growth [31]. In addition, PA can influence epigenetic regulation by modulating DNA methylation and protecting tumor suppressor genes [32]. However, excessive PA has been associated with immune dysfunction, increased inflammation, and oxidative stress, which may partly explain the lack of a clear protective effect in the moderate and high NOPA groups [33]. The subgroup-specific protective effect of low NOPA observed in smokers and those with lower BMI suggests that PA may exert greater benefits in populations with elevated baseline risks. For smokers, in particular, PA could counteract the pro-tumorigenic effects of tobacco-related inflammation and oxidative stress [34]. For those with BMI < 25, PA may mitigate the adverse consequences of low BMI, such as sarcopenia and reduced physiological reserve, thereby enhancing its protective association with CRC [35]. In younger individuals, the longer latency period for CRC development may allow the protective role of PA to manifest more clearly. These findings suggest that PA recommendations for CRC prevention may benefit from risk-adapted tailoring rather than a one-size-fits-all approach. Incorporating participant characteristics when advising on PA could enhance preventive impact. Regarding the combined effect of SB and PA on CRC risk, only individuals who were both physically active and engaged in short SB showed a significantly reduced HR, indicating a combined effect of two behaviors. While prolonged sedentary time may sustain systemic inflammation, PA alone may not fully overcome this adverse pathway. In contrast, the combination of reduced SB and sufficient PA can maximize anti-inflammatory and metabolic benefits, leading to a stronger protective effect [1,36]. This highlights the need for integrated interventions that simultaneously promote PA and limit SB, rather than targeting either behavior in isolation. This study has some limitations. First, PA and SB were assessed through self-reports, which may introduce recall bias. However, the use of a structured questionnaire administered by trained interviewers helped minimize such bias. Second, information regarding specific types of PA was not collected; therefore, direct comparison with previous studies may be limited. Nevertheless, the use of standardized PA categories across all participants ensures internal consistency for valid comparisons within the cohort. Third, women were not included in the analysis due to the limited number of CRC cases, which made it difficult to achieve sufficient statistical power, thereby restricting the generalizability of the findings to male populations. Further studies are needed to determine whether the observed associations also apply to women. Despite these limitations, this study has several strengths. First, it examined the relationship between PA and CRC risk in a large-scale prospective cohort of the Korean population, which has been underrepresented in previous research predominantly conducted in Western populations. This contributes to expanding ethnic and regional diversity in the current understanding of the protective role of PA in CRC incidence. The prospective design also minimizes reverse causation and helps clarify the temporal relationship between PA and CRC incidence. Second, the study subjects were stratified by various demographic and behavioral factors, revealing differential associations. Few studies have evaluated the effect of PA on CRC with stratification analyses, making the findings from this study valuable for setting the guidelines for targeted public health strategies to promote PA. Furthermore, the use of a standardized and validated questionnaire across all participants ensured consistency in PA and SB assessment, supporting the reliability of the findings. Conclusion In conclusion, this prospective cohort study demonstrated that engaging in NOPA of 300–599 MET min/week was associated with a lower risk of CRC, particularly among younger individuals, smokers, and those with lower BMI. The protective effect was most evident when sufficient PA was combined with short SB. These findings support the role of PA as a modifiable factor for CRC prevention and highlight the importance of considering individual factors in developing public health strategies. Abbreviations CRC: Colorectal cancer PA: Physical Activity SB: Sedentary Behavior HR: Hazard Ratio CI: Confidence Interval BMI: Body Mass Index NOPA: Non-occupational Physical Activity LPA: Leisure-time Physical Activity OPA: Occupational Physical Activity KMCC: Korean Multi-Center Cancer Cohort MET: Metabolic Equivalents of Task Declarations Ethics approval and consent to participate All participants in the KMCC had provided written informed consent and the study protocols were approved by the International Review Board of Seoul National University Hospital (IRB no: 0110-084-002). This study was conducted in accordance with the principles of the Declaration of Helsinki and adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Consent for publication Not applicable. Availability of data and materials The datasets analyzed during this study are not publicly available due to participant privacy and institutional regulations. However, the data are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding No funding was obtained for this study. Authors' contributions Study conception and design: S.E.P and S.K.P; data collection: S.L and S.K.P; analysis and interpretation of results: S.E.P, S.S and S.K.P; drafting the manuscript: S.E.P; critical revision of the article: S.E.P, Y.H, W.L, S.M, M.H.K, J.Y.C and S.K.P; all authors discussed the results and contributed to the final manuscript. The authors read and approved the final manuscript. Acknowledgements This study was supported by a grant from Seoul National University Hospital (2025). This study was supported by the National R&D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health & Welfare, Republic of Korea (HA21C0140). Author information Se Eun Park: https://orcid.org/0009-0002-7679-7071 / [email protected] Soseul Sung: https://orcid.org/0000-0002-5801-3379 / [email protected] Sangjun Lee: https://orcid.org/0000-0003-4080-0494 / [email protected] Youjin Hong: https://orcid.org/0000-0002-3978-0214 / [email protected] Woojin Lim: https://orcid.org/0000-0001-8305-0246 / [email protected] Sungji Moon: https://orcid.org/0000-0002-6668-3065 / [email protected] Min-Hyung Kim: https://orcid.org/0000-0002-0072-2631 / [email protected] Ji- Yeob Choi: https://orcid.org/0000-0001-5365-8189 / [email protected] Sue K. Park: https://orcid.org/0000-0001-5002-9707 / [email protected] References An S, Park S. Association of Physical Activity and Sedentary Behavior With the Risk of Colorectal Cancer. J Korean Med Sci. 2022;37(19):e158. Douaiher J, Ravipati A, Grams B, Chowdhury S, Alatise O, Are C. Colorectal cancer—global burden, trends, and geographical variations. J Surg Oncol. 2017;115(5):619-630. National Cancer Information Center of Korea. Incidence rate for 10 leading cancer types. https://cancer.go.kr/lay1/S1T639C641/contents.do. Accessed 22 June 2025. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. Friedenreich CM, Ryder-Burbidge C, McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Mol Oncol. 2021;15(3):790-800. Sung S, Moon S, An J, Jung J, Lee HS, Hong Y, et al. Preventable cancer cases and deaths attributable to deficit of physical activity in Korea from 2015 to 2030. Epidemiol Health. 2025;47:e2025010. Strath SJ, Kaminsky LA, Ainsworth BE, Ekelund U, Freedson PS, Gary RA, et al. Guide to the assessment of physical activity: Clinical and research applications: a scientific statement from the American Heart Association. Circulation. 2013;128(20):2259-79. Kerr J, Anderson C, Lippman SM. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol. 2017;18(8):e457-e471. Moore SC, Lee IM, Weiderpass E, Campbell PT, Sampson JN, Kitahara CM, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016;176(6):816-25. Stamatakis E, Ahmadi MN, Friedenreich CM, Blodgett JM, Koster A, Holtermann A, et al. Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults: The UK Biobank Accelerometry Study. JAMA Oncol. 2023;9(9):1255-1259. Sung JH, Son SR, Baek SH, Kim BJ. Association of occupation with the daily physical activity and sedentary behaviour of middle-aged workers in Korea: a cross-sectional study based on data from the Korea National Health and Nutrition Examination Survey. BMJ Open. 2021;11(11):e055729. Pham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012;42(1):2-13. Odegaard AO, Koh WP, Yuan JM. Combined lifestyle factors and risk of incident colorectal cancer in a Chinese population. Cancer Prev Res (Phila). 2013;6(4):360-7. Khil H, Kim SM, Hong S, Gil HM, Cheon E, Lee DH, et al. Time trends of colorectal cancer incidence and associated lifestyle factors in South Korea. Sci Rep. 2021;11(1):2413. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164. Choi J, Badowski G, Shvetsov YB, Dulana L, Teria R, Jin SB, et al. Disparities in Colorectal Cancer Incidence among Asian and Pacific Islander Populations in Guam, Hawai'i, and the United States. Int J Environ Res Public Health. 2024;21(2):170. Sung S, An J, Jung J, Lee HS, Moon S, Kim I, et al. Preventable cancer cases and deaths attributable to tobacco smoking in Korea from 2015 to 2030. Epidemiol Health. 2025; 47:e2025008. Sung S, An J, Jung J, Lee HS, Moon S, Kim I, et al. Preventable cancer cases and deaths attributable to alcohol consumption in Korea from 2015 to 2030. Epidemiol Health. 2025;47:e2025009. Hong Y, An J, Jung J, Lee HS, Sung S, Moon S, et al. Comparison of Population Attributable Fractions of Cancer Incidence and Mortality Linked to Excess Body Weight in Korea from 2015 to 2030. Endocrinol Metab (Seoul). 2024;39(6):921-931. World Cancer Research Fund; American Institute for Cancer Research. Diet, nutrition, physical activity and cancer: colorectal cancer. https://www.wcrf.org/wp-content/uploads/2024/10/Colorectal-cancer-report.pdf. Accessed 22 June 2025. Yoo KY, Shin HR, Chang SH, Lee KS, Park SK, Kang D, et al. Korean Multi-center Cancer Cohort Study including a Biological Materials Bank (KMCC-I). Asian Pac J Cancer Prev. 2002;3(1):85-92. Lee S, Ko KP, Lee JE, Kim I, Jee SH, Shin A, et al. The Korea Cohort Consortium: the future of Pooling Cohort Studies. J Prev Med Public Health. 2022;55(5):464-474. Giovannucci E, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control. 1996;7(2):253-63. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381-95. Li Y, Zhou Q, Luo X, Li H, Feng Y, Zhao Y, et al. Association between sedentary time and 6-year all-cause mortality in adults: the Rural Chinese Cohort Study. J Nutr Health Aging. 2022;26(3):236-242. Patel AV, Bernstein L, Deka A, Feigelson HS, Campbell PT, Gapstur SM, et al. Leisure time spent sitting in relation to total mortality in a prospective cohort of US adults. Am J Epidemiol. 2010;172(4):419-29. International Agency for Research on Cancer. List of classifications by cancer sites with sufficient or limited evidence in humans. https://monographs.iarc.who.int/wp-content/uploads/2019/07/Classifications_by_cancer_site.pdf. Accessed 22 June 2025. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713-732. Amirsasan R, Akbarzadeh M, Akbarzadeh S. Exercise and colorectal cancer: prevention and molecular mechanisms. Cancer Cell Int. 2022;22(1):247. de Souza-Teixeira F, Alonso-Molero J, Ayán C, Vilorio-Marques L, Molina AJ, González-Donquiles C, et al. PGC-1α as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer. Cancer Prev Res (Phila). 2018;11(9):523-534. Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, et al. Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis. 2015;2(1):13-25. Fox F, Liu D, Breteler MMB, Aziz NA. Physical activity is associated with slower epigenetic ageing-Findings from the Rhineland study. Aging Cell. 2023;22(6):e13828. Nieman DC, Wentz LM. The compelling link between physical activity and the body's defense system. J Sport Health Sci. 2019;8(3):201-217. Bai X, Wei H, Liu W, Coker OO, Gou H, Liu C, et al. Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites. Gut. 2022;71(12):2439-2450. He J, Luo W, Huang Y, Song L, Mei Y. Sarcopenia as a prognostic indicator in colorectal cancer: an updated meta-analysis. Front Oncol. 2023;13:1247341. Lopes SR, Martins C, Santos IC, Teixeira M, Gamito É, Alves AL. Colorectal cancer screening: A review of current knowledge and progress in research. World J Gastrointest Oncol. 2024;16(4):1119-1133. Additional Declarations No competing interests reported. Supplementary Files AdditionalFile1.docx Table S1. Selected characteristics of cohort population and CRC cases Table S2. Participant characteristics by PA level in KMCC population Table S3. Participant characteristics by OPA in KMCC population Table S4. Distribution of occupation by NOPA percentile groups AdditionalFile2.tif Figure S1. Distribution of NOPA and OPA in KMCC population (NOPA, non-occupational physical activity; OPA, occupational physical activity; MET, Metabolic Equivalent of Task; KMCC, Korean Multi-center Cancer Cohort study). * Dotted blue line refers to the median number of frequencies. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 10 Nov, 2025 Reviewers agreed at journal 31 Oct, 2025 Reviewers invited by journal 31 Oct, 2025 Editor invited by journal 07 Oct, 2025 Editor assigned by journal 07 Oct, 2025 Submission checks completed at journal 07 Oct, 2025 First submitted to journal 06 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7788690","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":543049569,"identity":"b79f2ee8-5e7d-41cd-99d1-5550886c9678","order_by":0,"name":"Se Eun Park","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Se","middleName":"Eun","lastName":"Park","suffix":""},{"id":543049570,"identity":"403162d0-04d3-4f1e-b018-5c6f0afcdc92","order_by":1,"name":"Soseul Sung","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Soseul","middleName":"","lastName":"Sung","suffix":""},{"id":543049571,"identity":"b666e51b-5113-46c5-80c1-401c0cb0d078","order_by":2,"name":"Sangjun Lee","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sangjun","middleName":"","lastName":"Lee","suffix":""},{"id":543049572,"identity":"097fe17d-baf7-4347-b8b5-de70327a449e","order_by":3,"name":"Youjin Hong","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Youjin","middleName":"","lastName":"Hong","suffix":""},{"id":543049576,"identity":"936233c8-138f-4ff0-b266-007c99bc2cdc","order_by":4,"name":"Woojin Lim","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Woojin","middleName":"","lastName":"Lim","suffix":""},{"id":543049580,"identity":"14011eca-687d-4c24-a1e7-b5bac916c2bd","order_by":5,"name":"Sungji Moon","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sungji","middleName":"","lastName":"Moon","suffix":""},{"id":543049584,"identity":"ce421f2f-b002-4df0-9e40-d64e3fd496f0","order_by":6,"name":"Min-Hyung Kim","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Min-Hyung","middleName":"","lastName":"Kim","suffix":""},{"id":543049586,"identity":"ed17d520-2445-4175-b743-82248a8eb57c","order_by":7,"name":"Ji-Yeob Choi","email":"","orcid":"","institution":"Seoul National University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Ji-Yeob","middleName":"","lastName":"Choi","suffix":""},{"id":543049587,"identity":"9096166f-d153-4fd3-b5c7-7d1a9fc01840","order_by":8,"name":"Sue K. Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYPCCBDkYy4BoLcaka0lsIFqL/IzkYw9+7klLnz+7x4DhRw2DsXkDAS0GN9LSDXue5eRuuHPGgLHnGIOZzAFCWiRyzCR4DlTkbpDIMWDgbWCwkSDssPxvkn8OVKTLz8gxYPxLjBaGGzls0jwHchKADANmoC1mBLUYnHlmbixzIM1ww420gsMyxySMCTusPfnZwzcHkuWBQbfx4ZsaG8MZBB3GwMAGZx1gYCDsE1Qto2AUjIJRMAqwAgCTNjsTWawEgQAAAABJRU5ErkJggg==","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Sue","middleName":"K.","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2025-10-06 06:53:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7788690/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7788690/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95806496,"identity":"02218565-ae28-42af-9597-c88785cbd2d5","added_by":"auto","created_at":"2025-11-13 08:47:32","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55015,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/c7043d8bcd59ea38e9a4f525.docx"},{"id":95806494,"identity":"e9d62702-1e63-4d11-9bcc-cf64fc3c1919","added_by":"auto","created_at":"2025-11-13 08:47:32","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":345858,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/26655e2ad591a6fcdda83b76.tif"},{"id":95806360,"identity":"ceb92ede-e131-442d-9af1-0aa4049a40ce","added_by":"auto","created_at":"2025-11-13 08:47:25","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":417954,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/ef7866f7472266672ff62f27.tif"},{"id":95806504,"identity":"5158f761-04ee-4004-b26c-ad140c5f8409","added_by":"auto","created_at":"2025-11-13 08:47:33","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":365496,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/f44d4392813d10b6cefbf5d7.tif"},{"id":95806616,"identity":"b7a4e5d4-c761-4e4c-9685-6f69d1cfe55c","added_by":"auto","created_at":"2025-11-13 08:47:43","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":642476,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/45dbe6a32c5391fc5c19585c.tif"},{"id":95806384,"identity":"dc76766c-fcde-4cc7-a1ce-ffe4d0799e5e","added_by":"auto","created_at":"2025-11-13 08:47:27","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":167768,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/3e8c819178c6b96d88906919.tif"},{"id":95806226,"identity":"b79d936e-d2c7-453a-9b7b-117b0cd850f8","added_by":"auto","created_at":"2025-11-13 08:47:20","extension":"json","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10827,"visible":true,"origin":"","legend":"","description":"","filename":"6f4775a7f7ee48a2b5743a1615d53c67.json","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/6e9196212658458e6e51e39a.json"},{"id":95806497,"identity":"7ac71b83-190c-411b-8488-adbf2a90cf75","added_by":"auto","created_at":"2025-11-13 08:47:32","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":28737,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/5e90b180510457e435621839.docx"},{"id":95806229,"identity":"f980bf6a-8244-4337-b1e4-99e358b735df","added_by":"auto","created_at":"2025-11-13 08:47:20","extension":"tif","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":709444,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/4d23576c93fe43a7bb54c456.tif"},{"id":95806416,"identity":"cf0b257a-4fb3-4a7a-b193-298a84f4fd9d","added_by":"auto","created_at":"2025-11-13 08:47:28","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":107412,"visible":true,"origin":"","legend":"","description":"","filename":"6f4775a7f7ee48a2b5743a1615d53c671enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/e7019cdb24f8b4201f9cf505.xml"},{"id":95806295,"identity":"e8cd0c73-bb2d-4f94-8e0f-bb44d75c6adf","added_by":"auto","created_at":"2025-11-13 08:47:22","extension":"tif","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":345858,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/34755f6ee7c5e286452cc343.tif"},{"id":95806499,"identity":"265382c3-5131-4ea4-adb1-59c1774eb92a","added_by":"auto","created_at":"2025-11-13 08:47:33","extension":"tif","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":417954,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/346500d6da97ea33ed3614cb.tif"},{"id":95818725,"identity":"0603d21d-8660-4ad0-a6a6-2c4b6ff71472","added_by":"auto","created_at":"2025-11-13 10:31:29","extension":"tif","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":365496,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/ad069d49346ad2ea93d95f53.tif"},{"id":95806552,"identity":"1ee626d4-20fd-4fa1-ae1e-d2b2a24d2d6c","added_by":"auto","created_at":"2025-11-13 08:47:35","extension":"tif","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":642476,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/9a7324a68b7df90bb146d309.tif"},{"id":95806582,"identity":"6f01d609-f259-4688-97d9-f98d8e9e884a","added_by":"auto","created_at":"2025-11-13 08:47:40","extension":"tif","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":167768,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/e4aa60cd599aaa831da4879b.tif"},{"id":95806373,"identity":"6f7f95e4-2351-4462-be20-b30cc9202fae","added_by":"auto","created_at":"2025-11-13 08:47:26","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38003,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/2cc202420dd7949be6fab51e.png"},{"id":95806374,"identity":"cf64281d-8ab1-4606-b5e2-534d344c96f6","added_by":"auto","created_at":"2025-11-13 08:47:26","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":61665,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/b49355a95534612645ad7af7.png"},{"id":95806551,"identity":"bc9c5fec-a07b-4b1c-b1fa-2d8ad0aa5acf","added_by":"auto","created_at":"2025-11-13 08:47:34","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":57519,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/ba41ab738d7bd6ad2ec787d8.png"},{"id":95806413,"identity":"94bc0fe4-c9de-459f-9c2e-3b844cacd9a7","added_by":"auto","created_at":"2025-11-13 08:47:28","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86163,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/abf87d40aa881d30e024ae9e.png"},{"id":95806501,"identity":"f75f08cc-4260-4f27-9c7f-fa8602b69c4a","added_by":"auto","created_at":"2025-11-13 08:47:33","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19695,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/d48f20343f4b4d1880c0bf15.png"},{"id":95806221,"identity":"38345bda-5feb-4664-afb7-190f1afcaa84","added_by":"auto","created_at":"2025-11-13 08:47:20","extension":"xml","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104975,"visible":true,"origin":"","legend":"","description":"","filename":"6f4775a7f7ee48a2b5743a1615d53c671structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/a1b8d1e3914b7f7fb065173d.xml"},{"id":95806488,"identity":"079c0e1e-181c-4df0-b875-869fd8869893","added_by":"auto","created_at":"2025-11-13 08:47:32","extension":"html","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":116607,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/764351d68047e40f23978e66.html"},{"id":95806294,"identity":"6e67b561-36fc-411e-aeb7-efebe1d31b6a","added_by":"auto","created_at":"2025-11-13 08:47:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":238511,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of study subjects.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/19aec05357dc7e768d0672de.png"},{"id":95806629,"identity":"79cfbf36-773a-447d-8b36-9895d654687a","added_by":"auto","created_at":"2025-11-13 08:47:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":250791,"visible":true,"origin":"","legend":"\u003cp\u003eThe probability of CRC incidence according to NOPA categories (MET min/week) in KMCC population (CRC, colorectal cancer; NOPA, non-occupational physical activity; MET, Metabolic Equivalent of Task; KMCC, Korean Multi-center Cancer Cohort).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/6be7e11d2f2fb60524dca792.png"},{"id":95806579,"identity":"3966fe82-3376-4ae8-aeaa-4dec7008e2ce","added_by":"auto","created_at":"2025-11-13 08:47:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":617148,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between MET min/week and ln (HR) in KMCC population (NOPA, non-occupational physical activity; OPA, occupational physical activity; MET, Metabolic Equivalent of Task; HR, hazard ratio; KMCC, Korean Multi-center Cancer Cohort study).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/60b71a535a70a19d4eda888a.png"},{"id":95806549,"identity":"2eb1337a-5a3e-4f81-a7ed-b3c508491399","added_by":"auto","created_at":"2025-11-13 08:47:34","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1747194,"visible":true,"origin":"","legend":"\u003cp\u003eMultivariable adjusted HRs for CRC incidence according to NOPA categories, stratified by subgroups (HR, hazard ratio; CRC, colorectal cancer; NOPA, non-occupational physical activity; MET, Metabolic Equivalent of Task; BMI, Body Mass Index). NOPA was categorized as inactive (\u0026lt;300), low (300–599), moderate (600–2,999), high (≥ 3,000 MET min/week). HR were adjusted for age, cigarette smoking, education, alcohol drinking and BMI.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/8fd44e192f90f9151440e0e9.png"},{"id":95806422,"identity":"a32fdc3a-f1b5-400d-86f1-ea2b68f2abbe","added_by":"auto","created_at":"2025-11-13 08:47:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":373337,"visible":true,"origin":"","legend":"\u003cp\u003eMultivariable adjusted HRs for CRC incidence according to combined effect of NOPA and SB (NOPA, non-occupational physical activity; SB, sedentary behavior; HR, hazard ratio; CRC, colorectal cancer;). NOPA was categorized as inactive (\u0026lt; 300 MET min/week) and active (≥ 300 MET min/week) and SB was classified as prolonged (≥ 6 hour/day) and short (\u0026lt; 6 hour/day). HRs were adjusted for age, cigarette smoking, education, alcohol drinking and BMI.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/fa39da945d474c3508beb622.png"},{"id":96239148,"identity":"5c4ce1ad-f079-4f84-a83b-720cd555ffa1","added_by":"auto","created_at":"2025-11-19 07:03:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4394299,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/8f01239f-08ee-46a9-8824-b04bb14e365c.pdf"},{"id":95806541,"identity":"f827564d-9605-4646-bd58-71429433dbab","added_by":"auto","created_at":"2025-11-13 08:47:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28737,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable S1.\u003c/strong\u003e Selected characteristics of cohort population and CRC cases\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable S2.\u003c/strong\u003e Participant characteristics by PA level in KMCC population\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable S3.\u003c/strong\u003e Participant characteristics by OPA in KMCC population\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable S4.\u003c/strong\u003e Distribution of occupation by NOPA percentile groups\u003c/p\u003e","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/e985293fc4fa6bfba96dbb20.docx"},{"id":95806585,"identity":"27957c8d-024f-4330-9e90-59cd190618e1","added_by":"auto","created_at":"2025-11-13 08:47:41","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":709444,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure S1.\u003c/strong\u003e Distribution of NOPA and OPA in KMCC population (NOPA, non-occupational physical activity; OPA, occupational physical activity; MET, Metabolic Equivalent of Task; KMCC, Korean Multi-center Cancer Cohort study). * Dotted blue line refers to the median number of frequencies.\u003c/p\u003e","description":"","filename":"AdditionalFile2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7788690/v1/1dcada9f662fd56583d34e2f.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort","fulltext":[{"header":"Background","content":"\u003cp\u003eGlobally, colorectal cancer (CRC) ranks third in cancer incidence with more than 1.9\u0026nbsp;million new cases, and it is the second leading cause of cancer-related deaths [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. By 2035, the number of CRC incidence is expected to increase by 80% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In South Korea, CRC was the second most diagnosed cancer in 2021, showing an annual increase of 2.6% from 2019 to 2021 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Numerous recent studies report a rising incidence of CRC among younger adults (under 50 years at diagnosis) in developed countries, highlighting the urgent need for further studies on the risk factors associated with CRC [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePhysical activity (PA) has consistently been suggested as a risk reduction factor for CRC in previous studies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PA is defined as any bodily movement that requires energy expenditure through the use of skeletal muscles and can be classified into four domains: leisure-time PA (LPA), occupational PA (OPA), domestic PA, and transportation PA [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Guidelines for PA emphasize LPA since it is known to be the most influential factor related to cancer incidence [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Several studies have demonstrated that an increase in moderate-to-vigorous LPA is associated with a reduced CRC risk [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, evidence regarding how subgroup characteristics influence the association between PA and CRC, and how PA interacts with sedentary behavior (SB) in relation to CRC risk, remains limited. Demographic factors of study subjects, such as age, occupation and body mass index (BMI), should be considered as potential effect modifiers due to differences in PA distribution [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMost studies addressing PA as a protective factor against CRC have been conducted primarily in Western populations [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, the association between PA and CRC may vary depending on individual characteristics, which differ between Western and Eastern populations [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Previous studies have identified racial disparities in CRC incidence linked to variations in risk factor prevalence and socioeconomic status [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These findings highlight the need for research specifically targeting Korean populations, where such risk factors may interact differently with PA. Stratification by lifestyle factors such as smoking, excess body weight and SB\u0026mdash;major contributors to cancer burden in Korea\u0026mdash;may clarify how these variables interact with PA in influencing CRC risk [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOverall, it is important to evaluate the association between PA and CRC in Korean populations, explore subgroup-specific associations through stratified analyses, and assess the combined effect of PA and SB on CRC risk. Given that PA is a modifiable lifestyle factor, identifying its protective effects across different risk profiles could contribute to reducing the burden of CRC in Korea [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cem\u003eStudy population and data collection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted within the Korean Multi-Center Cancer Cohort (KMCC) as a prospective cohort study. A total of 20,631 participants were enrolled from 1993 to 2005 across seven rural and urban areas in Korea: Haman, Uiryeong, Chuncheon, Chungju, Pohang, Uljin, and Changwon [21].\u0026nbsp;The subject selection flowchart for the total cohort is shown in Figure 1. We excluded participants with a history of cancer (n=623), insufficient information on BMI and PA (n=8,646) and women (n=6,687)\u0026nbsp;because the number of CRC cases was insufficient for reliable statistical analyses.\u0026nbsp;Consequently, the final cohort for analysis comprised 4,675 male subjects.\u0026nbsp;Data on general lifestyle, PA, SB and agricultural exposure were collected through interviews conducted by trained interviewers using a structured questionnaire and anthropometric measurements were also gathered [22].\u0026nbsp;Incident cancer cases at KMCC were identified through record linkage with data from the National Cancer Registry.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eExposure assessment: Physical activity and sedentary behavior\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eInformation on the level of PA was collected using an interview-based questionnaire. The questionnaire classified PA into three categories: vigorous non-occupational PA (NOPA), moderate NOPA and OPA. Vigorous NOPA included jogging, cycling uphill, playing tennis, participating in swimming competitions, and engaging in aerobic activities. Moderate NOPA included activities such as walking briskly, playing golf or bowling, riding a bicycle on level roads, gardening, cleaning, and doing laundry. OPA was defined as activities such as moving heavy furniture, loading and unloading trucks, shoveling, planting rice, and weeding.\u003c/p\u003e\n\u003cp\u003eThe questionnaire was designed to assess the level of PA based on activity time ranging from less than 0.5 hours per week to 31 hours or more per week. Metabolic equivalents of tasks (METs) were used to evaluate overall PA level. 1 MET is defined as 3.5 mL of oxygen uptake per kilogram per minute when a person is sitting quietly [23]. METs were calculated by multiplying the average number of minutes per week of each PA by the specific MET score according to the IPAQ standard [24]. Vigorous NOPA and OPA were assigned a value of 8 METs, while moderate NOPA was assigned a value of 4 METs. After estimating METs, respondents were categorized into quartiles based on the interquartile range of the distribution for NOPA: \u0026lt; 300 (reference), 300\u0026ndash;599, 600\u0026ndash;2,999, and \u0026ge; 3,000. This approach allowed us to examine relationships across the full spectrum of activity levels observed in our cohort. For OPA, the highest category (\u0026ge; 3,000 MET minutes/week) was further divided at 9,000 MET minutes/week, resulting in the following categories: \u0026lt; 300 (reference), 300\u0026ndash;599, 600\u0026ndash;2,999, 3,000\u0026ndash;8,999, and \u0026ge; 9,000. For the analysis of the combined effects of PA and SB, PA was classified into two groups: inactive (\u0026lt; 300 MET min/week) and active (\u0026ge; 300 MET min/week). SB was defined based on self-reported television viewing time, with \u0026ge; 6 hours/day categorized as prolonged and \u0026lt; 6 hours/day as short, according to previous studies [25,26].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe baseline differences among four MET min/week groups were compared using linear regression for continuous variables and Cochran-Armitage test for categorical variables. Differences in mean age and BMI, along with occupation (farmer/non-farmer), cigarette smoking (never/ever), alcohol consumption (never/ever), educational level (\u0026ge; 9 years), family history of CRC, colon polyps or irritable bowel syndrome, diabetes, meat preference and dietary intake were evaluated.\u003c/p\u003e\n\u003cp\u003eThe Cox proportional hazards model was used to evaluate hazard ratios (HRs) and their 95% confidence intervals (95% CIs) for CRC incidence based on the level of PA. The following factors were selected as potential confounders in the model: (a) age, educational level, and BMI, which may affect lifestyle factors including PA; (b) cigarette smoking as a Group 1A carcinogenic agent according to the International Agency for Research on Cancer [27]; and (c) alcohol drinking as a risk factor for CRC with convincing evidence [28].\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eCharacteristics of study subjects and distribution of PA\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSelected characteristics are presented in Table 1. A significant trend was observed across NOPA levels (MET min/week) for occupation, smoking status, alcohol consumption and vegetable intake. Selected characteristics of the cohort population and CRC cases revealed differences in age, education level, diabetes diagnosis and meat preference (S1 Table). Low and high groups of NOPA and OPA categories also showed significant differences for several characteristics (S2 Table). There was a marked trend (p \u0026lt; 0.05) among different characteristics including age, BMI, occupation, smoking status, education level, diabetes diagnosis and vegetable intake across OPA levels (S3 Table). Farmers were more common in the NOPA \u0026gt; 90th percentile group compared with the lower percentile groups (S4 Table). The distribution of NOPA and OPA differed with the trend of NOPA showing a downward-sloping curve, whereas OPA exhibited an inverse J-shaped curve (S1 Figure).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAssociation between PA and incidence of CRC\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAssociation between the PA level and incidence of CRC is presented in Table 2. In NOPA, the 300\u0026ndash;599 MET min/week group was significantly associated with a reduced risk of CRC incidence (HR=0.14, 95% CI=0.04\u0026ndash;0.61). OPA did not show any statistically significant relationships on CRC incidence. Figure 2 demonstrates that individuals in the 300\u0026ndash;599 MET min/week of NOPA group had the lowest cumulative incidence of CRC relative to the other groups (p \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003eFurther analyses are presented in Figures 3 to 5. As shown in Figure 3, restricted cubic spline analysis presented that the relationship between CRC incidence and NOPA differed from that with OPA. Figure 4 illustrates the stratified analysis of the association between PA and CRC incidence with HRs and 95% CIs in a forest plot. When NOPA was categorized into four groups (inactive as \u0026lt; 300, low as 300-599, moderate as 600-2,999 and high as \u0026ge; 3,000 MET min/week), analyses by age, occupation, smoking status, and BMI revealed that the low\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eSelected characteristics of total participants in KMCC according to METs of NOPA\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 150px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 763px;\"\u003e\n \u003cp\u003eMET (min/week)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026lt; 300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e300 \u0026ndash; 599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e600 \u0026ndash; 2999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u0026ge; 3000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e for trend\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eMean (SD)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eMean (SD)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eMean (SD)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eMean (SD)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e51.38 (15.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e51.66 (15.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e51.79 (15.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e53.22 (13.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e23.06 (3.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e23.35 (3.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e23.37 (3.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e23.51 (2.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eN (%)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eN (%)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eN (%)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eN (%)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eFarmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e606 (49.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e241 (44.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e757 (44.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e691 (56.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eEver-smoking\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e986 (80.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e448 (82.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e1,333 (79.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e982 (80.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eEver-alcohol drinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e953 (78.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e398 (73.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e1,259 (75.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e927 (76.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eEducation \u0026ge; 9 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e497 (40.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e211 (39.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e817 (48.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e639 (52.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eFamily history of CRC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10 (0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e6 (1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e15 (0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e12 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eColon polyps or IBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e8 (0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e2 (0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e9 (0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e5 (0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eDiabetes\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e123 (10.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e61 (11.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e186 (11.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e148 (12.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eMeat preference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e228 (55.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e104 (56.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e443 (59.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e280 (60.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eDietary intake\u0026nbsp;\u003cbr\u003e\u0026nbsp;(time/week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;Red meats \u0026ge; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e227 (57.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e103 (59.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e461 (65.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e291 (69.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;Vegetables \u0026ge; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e341 (69.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e163 (73.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e613 (72.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e407 (76.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;Fruits \u0026ge; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e272 (52.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e156 (59.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e635 (67.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e410 (69.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations; KMCC, Korean Multi-center Cancer Cohort study; MET, Metabolic Equivalent of Task; NOPA, non-occupational physical activity; BMI, Body mass index; CRC, colorectal cancer; IBD, irritable bowel syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1. Liner regression for continuous variables (age, BMI) and Cochran\u0026ndash;Armitage trend test for categorical variables (farmer, cigarettes smoking, alcohol drinking, education \u0026ge; 9 years, family history of CRC, colon polyps or IBD, diabetes, meat preference and dietary intake).\u003c/p\u003e\n\u003cp\u003e2. Ever-smoking is defined as past and current smoking more or equal to 400 cigarettes.\u003cbr\u003e\u0026nbsp;3. Diabetes was defined as \u0026lsquo;past diagnosis of diabetes mellitus\u0026rsquo; or \u0026lsquo;fasting blood sugar \u0026gt; 125 mg/mL\u0026rsquo;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eAssociation between MET min/week of PA and CRC risk\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eMET min/week\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eCohort\u003c/p\u003e\n \u003cp\u003ePerson-years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eCancers\u003c/p\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003eHR (95% CI)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNOPA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026lt; 300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e15089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e1.00 (reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e300-599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e6432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.14 (0.04-0.61)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e600-2999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e20320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e0.57 (0.03-2.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026ge; 3000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e15371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e0.77 (0.04-3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOPA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026lt; 300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e19484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e1.00 (reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e300-599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e4903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e1.06 (0.41-2.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e600-2999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e6145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e1.06 (0.35-3.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e3000-8999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e7487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e0.94 (0.33-2.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e\u0026ge; 9000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e19194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35px;\"\u003e\n \u003cp\u003e0.95 (0.36-2.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: MET, Metabolic Equivalent of Task; PA, physical activity; CRC, colorectal cancer; NOPA, non-occupational physical activity; OPA,\u0026nbsp;occupational\u0026nbsp;physical activity\u003cbr\u003e\u0026nbsp;1. Adjusted for age, cigarette smoking, education, alcohol drinking and BMI.\u003c/p\u003e\n\u003cp\u003eNOPA group was associated with a lower incidence of CRC among individuals aged \u0026lt; 65 years (HR=0.12, 95% CI=0.02\u0026ndash;0.86), smokers (HR=0.08, 95% CI=0.01\u0026ndash;0.60), and those with BMI \u0026lt; 25 (HR=0.12, 95% CI=0.02\u0026ndash;0.89). Figure 5 illustrates the combined effect of PA and SB on CRC incidence; compared with participants who had inactive PA and prolonged SB, those with active PA and short SB showed a reduced risk of CRC (HR=0.25, 95% CI= 0.08\u0026ndash;0.83).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study of 4,675 male participants, we observed engaging in NOPA of 300\u0026ndash;599 MET min/week was associated with a lower risk of CRC, while OPA showed no significant association. Stratified analyses further indicated that the protective effect of low NOPA in 300\u0026ndash;599 MET min/week group was evident among individuals aged \u0026lt; 6 years, smokers, and those with BMI \u0026lt; 25. In addition, combined analysis revealed that participants with active PA and shorter SB had a reduced risk of CRC compared with those with inactive PA and prolonged sedentary time.\u003c/p\u003e\n\u003cp\u003eThe biological mechanisms underlying the association between PA and CRC involve obesity, IGF-1 signaling, chronic inflammation, and epigenetic regulation [29]. Physical inactivity contributes to abdominal obesity, reduced insulin sensitivity, and systemic inflammation, thereby increasing CRC risk [30]. Insufficient PA may also elevate circulating IGF-1, promoting abnormal cell proliferation and tumor growth [31]. In addition, PA can influence epigenetic regulation by modulating DNA methylation and protecting tumor suppressor genes [32]. However, excessive PA has been associated with immune dysfunction, increased inflammation, and oxidative stress, which may partly explain the lack of a clear protective effect in the moderate and high NOPA groups [33].\u003c/p\u003e\n\u003cp\u003eThe subgroup-specific protective effect of low NOPA observed in smokers and those with lower BMI suggests that PA may exert greater benefits in populations with elevated baseline risks. For smokers, in particular, PA could counteract the pro-tumorigenic effects of tobacco-related inflammation and oxidative stress [34].\u0026nbsp;For those with BMI \u0026lt; 25, PA may mitigate the adverse consequences of low BMI, such as sarcopenia and reduced physiological reserve, thereby enhancing its protective association with CRC [35]. In younger individuals, the longer latency period for CRC development may allow the protective role of PA to manifest more clearly. These findings suggest that PA recommendations for CRC prevention may benefit from risk-adapted tailoring rather than a one-size-fits-all approach. Incorporating participant characteristics when advising on PA could enhance preventive impact.\u003c/p\u003e\n\u003cp\u003eRegarding the combined effect of SB and PA on CRC risk, only individuals who were both physically active and engaged in short SB showed a significantly reduced HR, indicating a combined effect of two behaviors. While prolonged sedentary time may sustain systemic inflammation, PA alone may not fully overcome this adverse pathway. In contrast, the combination of reduced SB and sufficient PA can maximize anti-inflammatory and metabolic benefits, leading to a stronger protective effect [1,36]. This highlights the need for integrated interventions that simultaneously promote PA and limit SB, rather than targeting either behavior in isolation.\u003c/p\u003e\n\u003cp\u003eThis study has some limitations. First, PA and SB were assessed through self-reports, which may introduce recall bias. However, the use of a structured questionnaire administered by trained interviewers helped minimize such bias. Second, information regarding specific types of PA was not collected; therefore, direct comparison with previous studies may be limited. Nevertheless, the use of standardized PA categories across all participants ensures internal consistency for valid comparisons within the cohort. Third, women were not included in the analysis due to the limited number of CRC cases, which made it difficult to achieve sufficient statistical power, thereby restricting the generalizability of the findings to male populations. Further studies are needed to determine whether the observed associations also apply to women.\u003c/p\u003e\n\u003cp\u003eDespite these limitations, this study has several strengths. First, it examined the relationship between PA and CRC risk in a large-scale prospective cohort of the Korean population, which has been underrepresented in previous research predominantly conducted in Western populations. This contributes to expanding ethnic and regional diversity in the current understanding of the protective role of PA in CRC incidence. The prospective design also minimizes reverse causation and helps clarify the temporal relationship between PA and CRC incidence. Second, the study subjects were stratified by various demographic and behavioral factors, revealing differential associations. Few studies have evaluated the effect of PA on CRC with stratification analyses, making the findings from this study valuable for setting the guidelines for targeted public health strategies to promote PA. Furthermore, the use of a standardized and validated questionnaire across all participants ensured consistency in PA and SB assessment, supporting the reliability of the findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this prospective cohort study demonstrated that engaging in NOPA of 300\u0026ndash;599 MET min/week was associated with a lower risk of CRC, particularly among younger individuals, smokers, and those with lower BMI. The protective effect was most evident when sufficient PA was combined with short SB. These findings support the role of PA as a modifiable factor for CRC prevention and highlight the importance of considering individual factors in developing public health strategies.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRC: Colorectal cancer\u003c/p\u003e\n\u003cp\u003ePA: Physical Activity\u003c/p\u003e\n\u003cp\u003eSB: Sedentary Behavior\u003c/p\u003e\n\u003cp\u003eHR: Hazard Ratio\u003c/p\u003e\n\u003cp\u003eCI: Confidence Interval\u003c/p\u003e\n\u003cp\u003eBMI: Body Mass Index\u003c/p\u003e\n\u003cp\u003eNOPA: Non-occupational Physical Activity\u003c/p\u003e\n\u003cp\u003eLPA: Leisure-time Physical Activity\u003c/p\u003e\n\u003cp\u003eOPA: Occupational Physical Activity\u003c/p\u003e\n\u003cp\u003eKMCC: Korean Multi-Center Cancer Cohort\u003c/p\u003e\n\u003cp\u003eMET: Metabolic Equivalents of Task\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll participants in the KMCC had provided written informed consent and the study protocols were approved by the International Review Board of Seoul National University Hospital (IRB no: 0110-084-002). This study was conducted in accordance with the principles of the Declaration of Helsinki and adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during this study are not publicly available due to participant privacy and institutional regulations. However, the data are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception and design: S.E.P and S.K.P;\u0026nbsp;data collection: S.L and S.K.P;\u0026nbsp;analysis and interpretation of results:\u0026nbsp;S.E.P, S.S and S.K.P;\u0026nbsp;drafting the manuscript:\u0026nbsp;S.E.P;\u0026nbsp;critical revision of the article: S.E.P,\u0026nbsp;Y.H, W.L, S.M, M.H.K, J.Y.C and S.K.P;\u0026nbsp;all authors discussed the results and contributed to the final manuscript. The authors read and approved the\u0026nbsp;final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a grant from Seoul National University Hospital (2025). This study was supported by the National R\u0026amp;D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health \u0026amp; Welfare, Republic of Korea (HA21C0140).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSe Eun Park: https://orcid.org/0009-0002-7679-7071 / [email protected]\u003c/p\u003e\n\u003cp\u003eSoseul Sung: https://orcid.org/0000-0002-5801-3379 / [email protected]\u003c/p\u003e\n\u003cp\u003eSangjun Lee: https://orcid.org/0000-0003-4080-0494 / [email protected]\u003c/p\u003e\n\u003cp\u003eYoujin Hong: https://orcid.org/0000-0002-3978-0214 / [email protected]\u003c/p\u003e\n\u003cp\u003eWoojin Lim: https://orcid.org/0000-0001-8305-0246 / [email protected]\u003c/p\u003e\n\u003cp\u003eSungji Moon: https://orcid.org/0000-0002-6668-3065 / [email protected]\u003c/p\u003e\n\u003cp\u003eMin-Hyung Kim: https://orcid.org/0000-0002-0072-2631\u0026nbsp;/\u0026nbsp;[email protected]\u003c/p\u003e\n\u003cp\u003eJi- Yeob Choi: https://orcid.org/0000-0001-5365-8189 / [email protected]\u003c/p\u003e\n\u003cp\u003eSue K. Park: https://orcid.org/0000-0001-5002-9707 / [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAn S, Park S. Association of Physical Activity and Sedentary Behavior With the Risk of Colorectal Cancer. J Korean Med Sci. 2022;37(19):e158.\u003c/li\u003e\n \u003cli\u003eDouaiher J, Ravipati A, Grams B, Chowdhury S, Alatise O, Are C. Colorectal cancer\u0026mdash;global burden, trends, and geographical variations. J Surg Oncol. 2017;115(5):619-630.\u003c/li\u003e\n \u003cli\u003eNational Cancer Information Center of Korea. Incidence rate for 10 leading cancer types. https://cancer.go.kr/lay1/S1T639C641/contents.do. Accessed 22 June 2025.\u003c/li\u003e\n \u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.\u003c/li\u003e\n \u003cli\u003eFriedenreich CM, Ryder-Burbidge C, McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Mol Oncol. 2021;15(3):790-800.\u003c/li\u003e\n \u003cli\u003eSung S, Moon S, An J, Jung J, Lee HS, Hong Y, et al. Preventable cancer cases and deaths attributable to deficit of physical activity in Korea from 2015 to 2030. Epidemiol Health. 2025;47:e2025010.\u003c/li\u003e\n \u003cli\u003eStrath SJ, Kaminsky LA, Ainsworth BE, Ekelund U, Freedson PS, Gary RA, et al. Guide to the assessment of physical activity: Clinical and research applications: a scientific statement from the American Heart Association. Circulation. 2013;128(20):2259-79.\u003c/li\u003e\n \u003cli\u003eKerr J, Anderson C, Lippman SM. Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol. 2017;18(8):e457-e471.\u003c/li\u003e\n \u003cli\u003eMoore SC, Lee IM, Weiderpass E, Campbell PT, Sampson JN, Kitahara CM, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016;176(6):816-25.\u003c/li\u003e\n \u003cli\u003eStamatakis E, Ahmadi MN, Friedenreich CM, Blodgett JM, Koster A, Holtermann A, et al. Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults: The UK Biobank Accelerometry Study. JAMA Oncol. 2023;9(9):1255-1259.\u003c/li\u003e\n \u003cli\u003eSung JH, Son SR, Baek SH, Kim BJ. Association of occupation with the daily physical activity and sedentary behaviour of middle-aged workers in Korea: a cross-sectional study based on data from the Korea National Health and Nutrition Examination Survey. BMJ Open. 2021;11(11):e055729.\u003c/li\u003e\n \u003cli\u003ePham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012;42(1):2-13.\u003c/li\u003e\n \u003cli\u003eOdegaard AO, Koh WP, Yuan JM. Combined lifestyle factors and risk of incident colorectal cancer in a Chinese population. Cancer Prev Res (Phila). 2013;6(4):360-7.\u003c/li\u003e\n \u003cli\u003eKhil H, Kim SM, Hong S, Gil HM, Cheon E, Lee DH, et al. Time trends of colorectal cancer incidence and associated lifestyle factors in South Korea. Sci Rep. 2021;11(1):2413.\u003c/li\u003e\n \u003cli\u003eSiegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164.\u003c/li\u003e\n \u003cli\u003eChoi J, Badowski G, Shvetsov YB, Dulana L, Teria R, Jin SB, et al. Disparities in Colorectal Cancer Incidence among Asian and Pacific Islander Populations in Guam, Hawai\u0026apos;i, and the United States. Int J Environ Res Public Health. 2024;21(2):170.\u003c/li\u003e\n \u003cli\u003eSung S, An J, Jung J, Lee HS, Moon S, Kim I, et al. Preventable cancer cases and deaths attributable to tobacco smoking in Korea from 2015 to 2030. Epidemiol Health. 2025; 47:e2025008.\u003c/li\u003e\n \u003cli\u003eSung S, An J, Jung J, Lee HS, Moon S, Kim I, et al. Preventable cancer cases and deaths attributable to alcohol consumption in Korea from 2015 to 2030. Epidemiol Health. 2025;47:e2025009.\u003c/li\u003e\n \u003cli\u003eHong Y, An J, Jung J, Lee HS, Sung S, Moon S, et al. Comparison of Population Attributable Fractions of Cancer Incidence and Mortality Linked to Excess Body Weight in Korea from 2015 to 2030. Endocrinol Metab (Seoul). 2024;39(6):921-931.\u003c/li\u003e\n \u003cli\u003eWorld Cancer Research Fund; American Institute for Cancer Research. Diet, nutrition, physical activity and cancer: colorectal cancer. https://www.wcrf.org/wp-content/uploads/2024/10/Colorectal-cancer-report.pdf. Accessed 22 June 2025.\u003c/li\u003e\n \u003cli\u003eYoo KY, Shin HR, Chang SH, Lee KS, Park SK, Kang D, et al. Korean Multi-center Cancer Cohort Study including a Biological Materials Bank (KMCC-I). Asian Pac J Cancer Prev. 2002;3(1):85-92.\u003c/li\u003e\n \u003cli\u003eLee S, Ko KP, Lee JE, Kim I, Jee SH, Shin A, et al. The Korea Cohort Consortium: the future of Pooling Cohort Studies. J Prev Med Public Health. 2022;55(5):464-474.\u003c/li\u003e\n \u003cli\u003eGiovannucci E, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control. 1996;7(2):253-63.\u003c/li\u003e\n \u003cli\u003eCraig CL, Marshall AL, Sj\u0026ouml;str\u0026ouml;m M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381-95.\u003c/li\u003e\n \u003cli\u003eLi Y, Zhou Q, Luo X, Li H, Feng Y, Zhao Y, et al. Association between sedentary time and 6-year all-cause mortality in adults: the Rural Chinese Cohort Study. J Nutr Health Aging. 2022;26(3):236-242.\u003c/li\u003e\n \u003cli\u003ePatel AV, Bernstein L, Deka A, Feigelson HS, Campbell PT, Gapstur SM, et al. Leisure time spent sitting in relation to total mortality in a prospective cohort of US adults. Am J Epidemiol. 2010;172(4):419-29.\u003c/li\u003e\n \u003cli\u003eInternational Agency for Research on Cancer. List of classifications by cancer sites with sufficient or limited evidence in humans. https://monographs.iarc.who.int/wp-content/uploads/2019/07/Classifications_by_cancer_site.pdf. Accessed 22 June 2025.\u003c/li\u003e\n \u003cli\u003eKeum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713-732.\u003c/li\u003e\n \u003cli\u003eAmirsasan R, Akbarzadeh M, Akbarzadeh S. Exercise and colorectal cancer: prevention and molecular mechanisms. Cancer Cell Int. 2022;22(1):247.\u003c/li\u003e\n \u003cli\u003ede Souza-Teixeira F, Alonso-Molero J, Ay\u0026aacute;n C, Vilorio-Marques L, Molina AJ, Gonz\u0026aacute;lez-Donquiles C, et al. PGC-1\u0026alpha; as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer. Cancer Prev Res (Phila). 2018;11(9):523-534.\u003c/li\u003e\n \u003cli\u003eDenduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, et al. Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis. 2015;2(1):13-25.\u003c/li\u003e\n \u003cli\u003eFox F, Liu D, Breteler MMB, Aziz NA. Physical activity is associated with slower epigenetic ageing-Findings from the Rhineland study. Aging Cell. 2023;22(6):e13828.\u003c/li\u003e\n \u003cli\u003eNieman DC, Wentz LM. The compelling link between physical activity and the body\u0026apos;s defense system. J Sport Health Sci. 2019;8(3):201-217.\u003c/li\u003e\n \u003cli\u003eBai X, Wei H, Liu W, Coker OO, Gou H, Liu C, et al. Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites. Gut. 2022;71(12):2439-2450.\u003c/li\u003e\n \u003cli\u003eHe J, Luo W, Huang Y, Song L, Mei Y. Sarcopenia as a prognostic indicator in colorectal cancer: an updated meta-analysis. Front Oncol. 2023;13:1247341.\u003c/li\u003e\n \u003cli\u003eLopes SR, Martins C, Santos IC, Teixeira M, Gamito \u0026Eacute;, Alves AL. Colorectal cancer screening: A review of current knowledge and progress in research. World J Gastrointest Oncol. 2024;16(4):1119-1133.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"epidemiology, colorectal neoplasms, cohort studies, physical activity, subgroup analysis, sedentary behavior","lastPublishedDoi":"10.21203/rs.3.rs-7788690/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7788690/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eColorectal cancer (CRC) is a significant and rising health burden globally and in Korea. While physical activity (PA) reduces CRC risk, evidence remains limited, especially in the Korean population. Additionally, the protective effect of PA may be modified by individual characteristics and is unclear in combination with sedentary behavior (SB). This study aimed to evaluate the association between PA and CRC risk in Korean populations, exploring subgroup-specific effects and the combined effect of PA and SB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eKorean Multi-Center Cancer Cohort included 20,631 participants from various regions. Of these subjects, 4,675 men completed a PA-related questionnaire at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence risk were estimated using multivariable Cox proportional hazards models. Models were adjusted for age, cigarette smoking, educational level, alcohol drinking, and body mass index (BMI). Stratified analyses were performed by individual characteristics (e.g., age, BMI, and smoking status) to assess effect modification. The relationship was further assessed considering the joint effect of PA and SB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eNon-occupational PA (NOPA) level of 300-599 MET min/week was associated with a decreased risk of CRC (HR=0.14, 95% CI=0.04–0.61) compared to the inactive NOPA group. Stratified analyses revealed that NOPA level of 300-599 MET was linked to lowered CRC risk in age \u0026lt; 65 group, smokers and BMI \u0026lt; 25 group (HR=0.12, 95% CI=0.02–0.86; HR=0.08, 95% CI=0.01–0.60; HR=0.12, 95% CI=0.02–0.89, respectively). Additionally, combined analysis indicated that individuals with active NOPA and short SB had a significantly lower risk of CRC compared to those with inactive NOPA and prolonged SB (HR=0.25, 95% CI=0.08–0.83).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis study indicates that NOPA of 300–599 MET min/week was associated with a reduced risk of CRC, particularly in younger individuals, smokers, and those with lower BMI. The protective effect was more evident when active NOPA was combined with short SB. These findings highlight PA as a modifiable factor in CRC prevention and the importance of incorporating individual characteristics into public health strategies.\u003c/p\u003e","manuscriptTitle":"Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 07:53:19","doi":"10.21203/rs.3.rs-7788690/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-11T04:30:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163591707648171510681669916906106307357","date":"2025-10-31T14:57:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-31T14:48:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-07T07:18:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-07T04:51:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-07T04:50:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-10-06T06:48:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0af0513d-ca0a-44ba-8040-a2c70a16027a","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-13T07:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-13 07:53:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7788690","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7788690","identity":"rs-7788690","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}